Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials

Abstract

Objectives: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes. We performed a meta-analysis to assess tirzepatide’s weight reduction efficacy and safety. Methods: We searched PubMed, Embase, and Cochrane for randomized controlled trials published from inception to July 2022, comparing tirzepatide with placebo for the co-primary endpoints of absolute and percent change in weight. Mean difference (MD) and odds ratio (OR) were calculated for continuous and binary outcomes, respectively. Review Manager 5.4.1 and RStudio were used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. Results: Of 397 search results, 6 studies (4036 participants) ranging from 12 to 72 weeks were included. Pooled analysis showed that tirzepatide 5 mg, 10 mg, and 15 mg were more effective than placebo, with MD in body weight of −7.7 kg (95% CI −11.0, −4.4; p < 0.001), −11.6 kg (95% CI −18.8, −4.3; p = 0.002), and −11.8 kg (95% CI −17.4, -6.2; p < 0.001), respectively, and MD in percent change in weight of −8.1% (95% CI −11.0, −5.2; p < 0.001), −11.9% (95% CI −18.1, −5.6; p < 0.001), and -12.4% (95% CI −17.2, −7.5; p < 0.001), respectively. Tirzepatide also reduced BMI and waist circumference. Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo. Conclusions: The results support that tirzepatide leads to substantial weight reduction and constitutes a valuable therapeutic option for weight management, despite an increase in gastrointestinal symptoms. Protocol registration: CRD42022348576.